Last update 01 Nov 2024

HSPH1

Last update 01 Nov 2024

Basic Info

Synonyms

Antigen NY-CO-25, heat shock 105kDa/110kDa protein 1, Heat shock 110 kDa protein

+ [9]

Introduction

Acts as a nucleotide-exchange factor (NEF) for chaperone proteins HSPA1A and HSPA1B, promoting the release of ADP from HSPA1A/B thereby triggering client/substrate protein release (PubMed:24318877). Prevents the aggregation of denatured proteins in cells under severe stress, on which the ATP levels decrease markedly. Inhibits HSPA8/HSC70 ATPase and chaperone activities (By similarity).

Drugs associated with HSPH1

HSPH1/sGC modulators(Hunan University)

Target

HSPH1 x sGC

Mechanism

HSPH1 modulators [+1]

Active Org.

Hunan University

Originator Org.

Hunan University

Active Indication

Pulmonary Arterial Hypertension

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

HLA-A24-restricted HSP105 peptide vaccine

Target

HSPH1

Mechanism

HSPH1 inhibitors

Active Org.

Japanese National Cancer Center

Originator Org.

Japanese National Cancer Center

Active Indication

Colorectal Cancer

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

HSP105 peptide-pulsed dendritic cell vaccine (Medinet)

Target

HSPH1

Mechanism

HSPH1 inhibitors

Active Org.-

Originator Org.

M Group Holdings Ltd.

Active Indication-

Inactive Indication

Neoplasms [+1]

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with HSPH1

100 Translational Medicine associated with HSPH1

0 Patents (Medical) associated with HSPH1

815

Literatures (Medical) associated with HSPH1

01 Dec 2024·European Journal of Medicinal Chemistry

Allosteric site identification, virtual screening and discovery of a sulfonamide Hsp110-STAT3 interaction inhibitor for the treatment of hypoxic pulmonary arterial hypertension

Article

Author: Hu, Liqing ; Zhao, Congke ; Gao, Ruizhe ; Hu, Yuanbo ; Tan, Wenhua ; Wu, Yan ; Wang, Yu ; Li, Qianbin ; Li, Mengqi

Pulmonary arterial hypertension (PAH) is a severe pulmonary vascular disorder marked by vascular remodeling, which is linked to the malignant phenotypes of pulmonary vascular cells. The prevailing therapeutic approaches for PAH tend to neglect the potential role of vascular remodeling, leading to the clinical prognosis remains poor. Previously, we first demonstrated that heat shock protein (Hsp110) was significantly activated to boost Hsp110-STAT3 interaction, which resulted in abnormal proliferation and migration of human pulmonary arterial endothelial cells (HPAECs) under hypoxia. In the present study, we initially postulated the allosteric site of Hsp110, performed a virtual screening and biological evaluation studies to discover novel Hsp110-STAT3 interaction inhibitors. Here, we identified compound 29 (AN-329/43448068) as the effective inhibitor of HPAECs proliferation and the Hsp110-STAT3 association with good druggability. In vitro, 29 significantly impeded the chaperone function of Hsp110 and the malignant phenotypes of HPAECs. In vivo, 29 remarkably attenuated pulmonary vascular remodeling and right ventricular hypertrophy in hypoxia-induced PAH rats (i.g). Altogether, our data support the conclusion that it not only provides a novel lead compound but also presents a promising approach for subsequent inhibitor development targeting Hsp110-STAT3 interaction.

01 Dec 2024·Molecular Biology Reports

CCT2 prevented β-catenin proteasomal degradation to sustain cancer stem cell traits and promote tumor progression in epithelial ovarian cancer

Article

Author: Jin, Danwen ; Hu, Qiong ; Chen, Jiayao ; Zhou, Chenhao

BACKGROUNDEpithelial ovarian cancer (EOC) is featured by rapid progression and dismal outcomes clinically. Chaperonin Containing TCP1 Subunit 2 (CCT2) was identified as a crucial regulator for tumor progression, however, its exact role in EOC remained largely unknown.METHODSCCT2 expression and prognostic value in EOC samples were assessed according to TCGA dataset. Proliferation and mobility potentials were assessed by CCK8, colony-formation, wound healing, and Transwell assays. Cancer stem cell (CSC) traits were evaluated by RT-PCR, WB assays, sphere-forming assay and chemoresistance analysis. Bioinformatic analysis, co-IP assays and ubiquitin assays were performed to explore the mechanisms of CCT2 on EOC cells.RESULTSCCT2 highly expressed in EOC tissues and predicted poor prognosis of EOC patients by TCGA analysis. Silencing CCT2 significantly restrained cell proliferation, migration, and invasion. Moreover, CCT2 could effectively trigger epithelial-mesenchymal transition to confer extensive invasion potentials to EOC cells, Importantly, CCT2 positively correlated with CSC markers in EOC, and CCT2 knockdown impaired CSC traits and sensitize EOC cells to conventional chemotherapy regimens. Contrarily, overexpressing CCT2 achieved opposite results. Mechanistically, CCT2 exerted its pro-oncogene function by triggering Wnt/β-catenin signaling. Specifically, CCT2 could recruit HSP105-PP2A complex, a well-established dephosphorylation complex, to β-catenin via direct physical interaction to prevent phosphorylation-induced proteasomal degradation of β-catenin, resulting in intracellular accumulation of active β-catenin and increased signaling activity.CONCLUSIONSCCT2 was a novel promotor for EOC progression and a crucial sustainer for CSC traits mainly by preventing β-catenin degradation. Targeting CCT2 may represent a promising therapeutic strategy for EOC.

01 Dec 2024·SLAS Technology

Deciphering the role of heat shock protein HSPA1L: biomarker discovery and prognostic insights in Parkinson's disease and glioma

Article

Author: Cheng, Hong ; Zhao, Yingjie ; Ling, Fang ; Wang, Jing ; Cao, Yasen ; Wang, Yixia ; Hou, Xiaoli

BACKGROUNDHeat shock proteins (HSPs) play a critical role in cellular stress responses and have been implicated in numerous diseases, including Parkinson's disease (PD) and various cancers. Understanding the differential expression and functional implications of HSPs in these conditions is crucial for identifying potential therapeutic targets and biomarkers for diagnosis and prognosis.METHODSWe utilized combined datasets (GSE6613 and GSE72267) to identify and analyze the heat shock-related genes differentially expressed in PD. Gene Set Variation Analysis (GSVA) was performed to explore functional profiles, while LASSO regression was employed to screen potential PD biomarkers. In glioma, prognostic value, immune infiltration, and pathway enrichment associated with HSPA1L gene expression were assessed via Kaplan-Meier plots, ssGSEA, and enrichment analyses.RESULTSIn PD, we identified 17 differentially expressed HSPs. Enrichment analysis revealed significant pathways related to protein homeostasis and cellular stress responses. LASSO regression pinpointed 12 genes, including HSPA1L, as significant markers for PD, with nomogram and calibration plots indicating predictive accuracy. Stratification based on HSPA1L expression in PD highlighted differentially active biological processes, immune responses, and metabolic disruptions. In the pan-cancer analysis, HSPA1L showed variable expression across cancer types and a significant correlation with patient survival and immune infiltration. In glioma, low HSPA1L expression was associated with worse overall survival, distinct immune infiltration patterns, and altered pathway activities.CONCLUSIONThis integrative study reveals the substantial role of HSPs, especially HSPA1L, in the pathogenesis and prognosis of PD and glioma. Our findings offer new perspectives on the molecular mechanisms underlying these diseases and propose HSPA1L as a potential prognostic biomarker and a target for therapeutic intervention.

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HSPH1

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